Mitochondrial diseases are genetic metabolic disorders characterized by mitochondrial dysfunction caused by genetic mutations. Those with selective muscle involvement are also known as simple mitochondrial myopathies, which mainly present with chronic progressive motor intolerance, muscle pain and muscle weakness, and can be accompanied by subclinical motor sensory peripheral neuropathy, while respiratory failure is relatively rare. Objective: We summarize 4 cases of mitochondrial myopathy with acute lactic acidosis, respiratory failure and limb weakness as the main manifestations, describe their clinical evolution, pathological features, electrophysiological manifestations and genetic diagnostic information, and summarize the clinical management experience. Typical cases: 4 patients, 1 male and 3 female, aged 30 years, 1 19 years and 2 14 years, respectively. All four patients presented with limb pain, tachycardia, shortness of breath, acute limb weakness, and loss of tendon reflexes, including transient lower limb swelling in two cases and acute abdominal pain in two cases; oliguria in one case; two cases were misdiagnosed as viral myocarditis and one case was misdiagnosed as Guillain-Barre syndrome. all four cases had exercise intolerance and no family history. All four cases had a sharp increase in blood lactate, with a peak of 12.8 mmol/L at the lowest and 30 mmol/L at the highest, and the blood gas was characterized by a sharp decrease in pH but a normal partial pressure of oxygen and a decrease in partial pressure of CO2. The muscle biopsies showed more than 5% fragmented red fibers, the number and structure of mitochondria were abnormal on electron microscopy, and crystalline inclusion bodies were found in one case. 4 cases had full gene sequencing of mitochondrial genes, and the A3243G mutation was clearly identified in 2 cases, the A8344G mutation in 1 case, and the unidentified mutation in 1 case. Two cases were treated with methylprednisolone injection without significant improvement, one case underwent tracheal intubation, two cases were treated with hemodialysis and CRT, and all four cases were given coenzyme Q10, B vitamins, and levocarnitine. The prognosis was that all three cases recovered to be able to go to work or school normally except for one case that died. In summary, the characteristics of severe mitochondrial myopathy are as follows: 1) youth or adolescents, subacute or acute onset, 2) weakness of limbs, muscle pain, shortness of breath, tachycardia, transient abdominal pain, swelling of lower limbs, 3) sudden weakness of limbs, loss of tendon reflexes, electromyography suggesting a significant decrease in motor nerve amplitude, which may be accompanied by sensory nerve involvement and slowed conduction velocity, 4) rapid increase in blood lactate The blood lactate is sharply elevated, pH is reduced but oxygen partial pressure is normal and CO2 partial pressure is reduced. 5. There is no family history of exercise intolerance in the past. 6. Hemodialysis treatment may be effective in the acute phase, and the prognosis is relatively good if the crisis can be overcome. Conclusion: Mitochondrial myopathy can present with acute lactic acidosis, respiratory failure and acute motor-sensory axonal neuropathy-like manifestations, which need to be differentiated from glycogen accumulation disease, lipid deposition myopathy and Green-Barre syndrome. The prognosis is relatively good if the risk period can be overcome.